Assessment of mutagenic potential of propoxur and its modulation by indole-3-carbinol.
Propoxur is a widely used dithiocarbamate pesticide. In the present set of investigations, mutagenicity of propoxur (in formulation) was studied using the micronucleus assay in bone marrow of Swiss mice. Single intraperitoneal (i.p.) administration of 25 mg/kg body weight dose of propoxur, which is a maximum tolerated dose (MTD), significantly induced the micronucleus formation in bone marrow cells after a 24- and 48-hr exposure. A half and a quarter of the MTD (12.5 and 6.25 mg/kg) were found ineffective to induce the micronuclei formation after 24- and 48-hr time periods by the i.p. route. However, the PCE:NCE ratio was inhibited significantly with all the dose levels at both time periods. Oral administration of propoxur at different dose levels also induced micronuclei formation. A single application of 50 and 25 mg/kg dose levels of propoxur, which are MTD and 50% of MTD, also significantly induced micronuclei formation after 24- and 48-hr time periods in bone marrow cells of Swiss mice as compared with solvent control group, whereas a 12.5 mg/kg dose of propoxur was ineffective in inducing micronuclei formation. Single application of indole-3-carbinol (I3C), a glucobrassicin derivative present in cruciferous vegetables, significantly inhibited the propoxur-induced micronuclei formation when it was given at the dose level of 500 mg/kg body weight 48 hr before the single application of propoxur. Therefore, it seems that propoxur is mutagenic in the above test systems and I3C inhibited the mutagenicity of propoxur significantly.
Agrawal
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RC
Laboratory of Environmental Carcinogenesis, Industrial Toxicology Research Center, Lucknow, India.
Mehrotra
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Nk
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D001074:Propoxur / Q000633:toxicity*
D016588:Anticarcinogenic Agents; D007211:Indoles; D007306:Insecticides; D001074:Propoxur; C016517:indole-3-carbinol